Feline infectious peritonitis virus (FIPV) induces a systemic infection in cats that is often fatal. The effusive form of the disease is characterized by accumulation of fibrinous ascitic fluid. The non-effusive form of the disease is characterized by granulomatous lesions in multiple organs including, but not limited to, liver, spleen, kidneys, lung, and intestines. Reviewed in Barlough, J. E. and C. A. Stoddart. Feline Coronaviral Infections in C. E. Greene (Ed.). Infectious Diseases of the Dog and Cats. W. B. Saunders Co., Philadelphia, Pa., 1990, pp. 300-312.
Feline infectious peritonitis virus is a coronavirus composed of three major structural proteins: The S (spike) protein, the E1 or M (transmembrane) protein, and the N (nucleocapsid) protein. Venema et al., Virology 181: 327-335, 1991 and Dale, et al., EPO 0,376,744.
Prior vaccines intended to prevent FIPV infection have actually been shown to exacerbate the disease caused by this virus. Pedersen, N. C. and J. W. Black, Am. J. Vet. Res. 44: 229-234, 1983; Vennema H., et al., J. Virol. 64: 1407-1409, 1990; Barlough, J. E., Can. J. Comp. Med. 49: 303-307, 1985; Barlough J. E. et al., Lab. Anim. Sci. 34: 592-597, 1984; Stoddart, C. A., et al., Res. Vet. Sci. 45: 383-388, 1988; and Pedersen, N. C., Adv. Vet. Sci. Comp. Med. 33: 413-428, 1989. This phenomenon apparently reflects an immune enhancement of infection mediated by immunoglobulins produced in response to the virus, in particular by those antibodies directed against the S protein. Olsen C. W. et al., J. Virol. 4: 175-189, 1981. Therefore, the best candidate vaccine for prophylaxis of this disease would be a preparation that induces strong cell-mediated immunity in the absence of enhancing antibodies. This could be accomplished with a vaccine that lacks the outer envelope protein but contains the other structural proteins of FIPV (N and E1). Prior attempts to vaccinate cats with a recombinant vaccinia virus expressing the N or E1 proteins of FIPV, however, have failed to induce strong protective immunity. Venema et al., Virology 181:327-335, 1991 and Dale, et al., European Patent Application 0,376,744. See also, Venema, European Patent Application 0,411,684.
What is needed in the art, therefore, is an effective vaccine against FIPV that utilizes the N and E1 proteins, or segments therefrom, as immunogens.